The requirement for continued gonadotropin (i.e., luteinizing hormone, LH) support to maintain primate luteal function is well established. Previous studies using rhesus monkeys determined that administration of the third generation antagonist of gonadotropin releasing hormone (GnRH) Antide at a dose of 3 mg/kg body weight beginning on day 6 of the luteal phase reduced serum progesterone below 1 ng/ml within 1 day. The present study was designed to determine the amount and frequency of LH replacement required to maintain luteal structure and function following GnRH antagonist treatment. Antide was administered concomitant with recombinant human LH (Ares Serono) at 8 hour intervals. Monkeys receiving 5 or 10 IU LH per injection had serum progesterone levels similar to control monkeys during the initial 4 days of treatment, while 20 IU LH per injection resulted in progesterone levels above those seen in controls. Monkeys receiving these fixed doses of LH mensed earlier than controls (day 14.0q0.7 versus day 16.3q0.3, p<0.05). However, replacement with an escalating pattern of LH (5-20 IU LH/injection) maintained normal serum progesterone levels throughout a luteal phase of normal length (day 16q1). To examine the effects of LH deprivation and replacement on luteal structure, luteal tissues were removed from monkeys receiving either Antide alone or Antide with the escalating pattern of LH replacement as described above. Corpora lutea from Antide-treated monkeys showed signs of structural luteolysis, while coadministration with the escalating pattern of LH replacement maintained luteal structure similar to time-matched controls. Administration of GnRH antagonist alone and with LH replacement provides a valuable model for studying gonadotropin-stimulated processes in the maintenance of the primate corpus luteum during the menstrual cycle.